Diabetes & Metabolism Journal

Original Articles

Impairment of Insulin Secretion by Fat Overload in Rat Pancreatic Islets and Effects of Antioxidants.: Chul Hee Kim, Chan Hee Kim, Hyeong Kyu Park, Kyo Il Suh, Ki Up Lee; Korean Diabetes J. 2002;26(5):347-356. Published online October 1, 2002

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Abstract PDF: BACKGROUND
It has recently been suggested that fat overload on pancreatic beta cells is responsible for the abnormal pattern of insulin secretion in type 2 diabetes mellitus. Antioxidant treatment was reported to preserve beta cell function in animal models of diabetes. This study was undertaken to examine the effects of various free fatty acids and triglyceride on insulin secretion in isolated rat pancreatic islets. In addition, we examined the effects of antioxidants. METHODS: Pancreatic islets of normal Sprague-Dawley rats were isolated by intraductal injection of collagenase and Ficoll-gradient centrifugation. The islets were treated with palmitat0e (C16:0), oleate (C18:1), linoleate (C18:2), and triglyceride emulsions (intralipid) for 72hours. Basal and glucose-stimulated insulin secretions were measured. The effects of the antioxidants, vitamin E, alpha-lipoic acid, and N-acetyl cysteine, were examined on the fat-induced change of insulin secretion. RESULTS: All of the free fatty acids and the triglyceride increased the basal insulin secretion. In contrast, insulin secretion stimulated by 27 mM glucose was significantly decreased after the treatment with free fatty acids or triglycerides. The antioxidant could not prevent the fat-induced inhibition of insulin secretion. CONCLUSION: These results show that various free fatty acids and triglyceride commonly cause defects in insulin secretion. However, we could not confirm the the hypothesis that increased oxidative stress may be involved in the pathogenesis of insulin secretory defect associated with fat overload.

Effects of Free Fatty Acids on Glutathione Redox Status in Cultured Endothelial Cells.: Joong Yeol Park, Chul Hee Kim, Yun Ey Chung, Hong Kyu Kim, Young Il Kim, Sung Kwan Hong, Jae Dam Lee, Ki Up Lee; Korean Diabetes J. 1998;22(3):262-270. Published online January 1, 2001

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Abstract PDF: BACKGROUND
Although plasma free fatty acids (FFA) are frequently elevated in diabetes mellitus, its role in the pathogenesis of diabetic vascular complications has not been well investigated. Recent stuclies reported that FFA may cause endothelial dysfunction through an enhancement of oxidative damage by decreasing glutathione redox cycle, an important anti-oxidant defense system in endothelial cells. In this study, we examined the effects of increased availability of FFA on intracellular glutathione redox cycle. METHODS: Bovine pulonary endothelial cells were exposed to 90 umol/L linoleic acid with or without 0.1 mM 2-bromopalmitate, an inhibitor of mitochondrial fatty acid oxidation, for 6hr. Components of the glutathione redox cycle such as total glutathione, reduced glutathione(GSH) and oxidized glutathione(GSSG) concentrations were measured by HPLC. RESULTS: Total glutathione concentration in cultured endothelial cells exposed to linoleic acid was significantly lower than that in control cells (10.8+ 0.5 vs 14.1+0.8 umol/g protein, P<0.05). Linoleic acid significantly decreased GSH concentrations (10.5+0.4 vs. 13.8+0.5 pmol/g protein, P<0.05) and the ratio of GSH/GSSG(26.3+1.3 vs. 47.0+2,1, P<0.05). Compared to cells exposed linoleic acid alone, total glutathione(13.5+0.5umol/g protein, P<0.05) and GSH concentration(13.2+0.4 pmol/g protein, P<0.05) significantly increased in cells treated with 2-bromopalmitate and linoleic acid. The ratio of GSH/GSSG in cells treated with 2-bromopalmitate and linoleic acid was higher th.an that in cells exposed to linoleic acid alone(44.1+1.3, P<0.05). CONCLUSION: Increased provision of FFA resulted in a derangement of glutathione redox cycle in cultured endothelial cells, which appears to be related to an increase in mitochondrial FFA oxidation. These results suggested that FFA can increase the risk of diabetic vascular complications.

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